International Journal of Pharmaceutical Investigation 2022-07-27T09:45:12+00:00 Editor, JPHI Open Journal Systems <p style="text-align: justify;"><strong>International Journal of Pharmaceutical Investigation</strong> publishing peer-reviewed scholarly reviews, themed issues and research articles within the entire scope of Pharmaceutical Sciences. The journal particularly aims to foster the dissemination of scientific information by publishing manuscripts related to current pharmaceutical drug delivery and related fields and submission of uninvited expert reviews and research articles in all areas of pharmaceutical drug delivery are welcomed. The journal publishes the following categories of manuscripts: research papers presenting original research, reviews, short communications, letter to the editor, commentaries, etc. including critical review articles providing a comprehensive analysis of research development within a defined area and editorial commentaries on key topical issues in pharmaceutical drug delivery.</p> <p style="text-align: justify;"><strong>Subjects covered in the journal</strong></p> <p style="text-align: justify;">The journal aims to cater for the latest outstanding developments in the field of Pharmaceutical Sciences and Technology covering the following topics (non-limiting):</p> <ul style="text-align: justify;"> <li class="show">Pharmaceutics</li> <li class="show">Nanotechnology</li> <li class="show">Current Novel Drug Delivery Systems</li> <li class="show">Quality control of Pharmaceuticals</li> <li class="show">Quality Assurance</li> <li class="show">National and International Regulatory Affairs</li> <li class="show">Validation Techniques</li> <li class="show">Industrial Pharmacy</li> <li class="show">Biopharmaceutics and Drug Disposition</li> <li class="show">Pharmacokinetics</li> <li class="show">Drug Development</li> <li class="show">Pharmaceutical Intellectual Property Rights.</li> </ul> <p style="text-align: justify;"><strong>Other Allied Pharmacy Subjects</strong></p> <ul> <li class="show" style="text-align: justify;">Pharmacognosy &amp; Ethnopharmacology</li> <li class="show" style="text-align: justify;">Pharm Chemistry &amp; Medicinal Chemistry&nbsp;</li> <li class="show" style="text-align: justify;">Pharmacology&nbsp;</li> <li class="show" style="text-align: justify;">Pharmacy Practice</li> <li class="show" style="text-align: justify;">Others</li> </ul> Threatened Ayurvedic Herb (Seeta Ashoka) Substitution Options for Menorrhagia-based on Bioactive Principle’s Molecular Docking Study 2022-07-27T07:44:08+00:00 Utkarsh Ghate Hema Kulkarni Manasi Deshpande Mandar Akkalkotkar <p style="text-align: justify;">Molecular docking studies are used to identify cultivated/ abundant herbs such as Coriander, Burmuda grass or Asparagus as potential replacement for Seeta Ashoka- <em>Saraca asoca </em>(Roxb.) De Wilde, syn. <em>S. indica </em>Linn. a rare Indian medicinal forest plant, threatened with extinction due to over harvest. Its bark is used to make the famous Ayurvedic medicine “<em>Ashokarishta</em>” to treat menorrhagia and as a uterine tonic like ergot but is mostly adulterated. We tested using molecular docking studies Quercetin and other polyphenols from Coriander as potent anti-inflammatory ingredients, similar to NSAID (Non-steroidal anti-inflammatory drugs).,<em> Polyalthia longifolia</em>, the common adulterant is also be noted to be effective as its bark contains 30-50% of tannin than <em>Saraca asoca</em>, so may help in thrombosis.</p> 2022-07-26T00:00:00+00:00 ##submission.copyrightStatement## Phytochemical Profiling and Antioxidant Potential of Coconut Inflorescence Sap 2022-07-27T07:44:09+00:00 Raseema Raheema Sharafudeen Annie Abraham Reshma Usha Soman <p style="text-align: justify;"><strong>Background:</strong> The coconut palm is so much more than just a tree; because all of this is essential with medicinal benefits. Coconut inflorescence sap (CIS) is the sweet, oyster-white colored, non-fermented juice tapped from the immature coconut spadix. Coconut products are widely used in Indian folk medicine for their effects on hemorrhaging, bronchitis, antimicrobial, radical scavenging, analgesics, anti-inflammation, anthelmintics, and immunotherapies. Many studies reported the fantastic health benefit of the coconut palm tree. The coconut inflorescence has cytoprotective and antihyperglycemic properties [Renjith, R.S. <em>et al.</em>, 2013]. But not many systematic studies have been conducted on Coconut Inflorescence Sap. The objective of the present study is to analyze the nutritional components, detect the mineral composition, perform preliminary phytochemical screening, and find out biologically active compounds using FTIR Spectrum analysis and LCMS analysis. <strong>Materials and</strong> <strong>Methods:</strong> CIS’s nutritional components and mineral content analysis were done following the standard procedures. The phytochemical screening, FTIR Spectrum analysis, and LCMS analysis are also done to confirm the health benefits of CIS. <strong>Results:</strong> CIS exhibited a significant amount of micro and macronutrients. The Phytochemical analysis also showed the presence of flavonoids, alkaloids, terpenes, steroids, phenols, and glycosides. The LCMS Spectrum analysis of CIS shows the presence of biologically significant compounds, namely 4-HydroxyCoumarin, P-Coumaric acid, Mellein, Leucopelargonidin, Coumarin, 3 Caffeoylquinic acid, Ferulic acid 4-O-Glucosidase and also three essential aminoacids L-Phenylalanine, L-isoleucine and D-Tryptophan. <strong>Conclusion:</strong> The nutritional composition, active phytochemical constituents, and polyphenolic compounds of CIS showed that CIS has a significant beneficial effect in upgrading the antioxidant status. CIS is a natural drink with effective antioxidant potential. Concerning the nutrient composition, mineral and amino acid composition, and scavenging assays, it would be possible to exploit this natural drink in clinical therapy.</p> 2022-07-26T00:00:00+00:00 ##submission.copyrightStatement## Virtual Screening of Potential Quorum Sensing Inhibitors of P. aeruginosa 2022-07-27T07:44:09+00:00 Snigdha Bhardwaj Pushpraj S Gupta <p style="text-align: justify;"><strong>Background: </strong>Pseudomonas aeruginosa (<em>P. aeruginosa</em>) is considered as one of the most opportunistic pathogens that may infect humans and led to increase in bacterial virulence or pathogenicity. <em>P. aeruginosa </em>exhibits variety of virulence factors and their rate of expression are associated with cell-to-cell communication process also known as quorum sensing (QS). LasR, a transcriptional factor which regulates the process of QS in <em>P. aeruginosa</em> is known as attractive drug target. <strong>Materials and Methods: </strong>The research work involves identification of putative inhibitors of LasR by molecular docking approach. Total 60 compounds were docked in the active site of LasR and CviR protein, followed by subsequent screening based on Lipinski’s rule of five, Veber rule and molar refractivity. <strong>Results: </strong>Out of 60 compounds, total seven novel compounds were selected on the basis of binding energies (docking score&gt; 10). Structures of LasRinhibitor complexes were analyzed to have vital insights from the binding between LasR and inhibitor molecules. The selected compounds were analyzed for physico-chemical properties and drug likeness to establish correlation between oral bioavailability and pharmacokinetics of compound.<strong> Conclusion:</strong> The study revealed the potential of thiazole derivative as novel QSI and expedite the possibility to combat virulence of multi-drug resistant <em>P. aeruginosa </em>in more effective manner.</p> 2022-07-26T00:00:00+00:00 ##submission.copyrightStatement## Synthesis, Characterization and Release Studies of Ethylene Diamine Tetraacetic Acid (EDTA)-Antimicrobial Drug Conjugates for Colon Release 2022-07-27T07:44:09+00:00 Anoop Kumar Ashutosh Mishra <p style="text-align: justify;"><strong>Background: </strong>The colon targeted drug delivery system is mainly useful for the topical treatment of colon diseases such as ulcerative colitis, Crohn’s disease OR colorectal cancers where we attain high local concentration and minimum side effects. In the present study we have synthesized some colon targeted Ethylene diamine tetra acetic acid (EDTA)-antimicrobial drug conjugates.<strong> Objectives</strong>: The goal of synthesizing EDTA-antimicrobial drug conjugates are that they reach intact in the colon and not be absorbed in the upper GIT, this is because of high molecular weight (&gt;500) of the conjugates (Lipinski’s rule of 5). <strong>Materials and Methods: </strong>A series of EDTA-antimicrobial drug conjugates (E1-E5) were synthesized by stirring tetra sodium EDTA with antimicrobial drugs viz. Metronidazole (MTZ), Ornidazole (OZ), Ciprofloxacin (CF), Norfloxacin (NF) and Sulfamethoxazole (SM) in presence of EDAC ((1-ethyl-3(3-dimethylaminopropyl) carbodiimide). All the synthesized conjugates were characterized by FTIR, NMR (1H and 13C), Mass spectrometry and elemental analysis to identify structural components. The synthesized conjugates were screened for antimicrobial (antibacterial) and colon release studies. <strong>Results and Discussion: </strong>On the basis of chemical and spectral analysis EDTA-antimicrobial drug conjugates were synthesized and synthesized conjugates showed good antimicrobial (antibacterial) activity against tested stains.<em> In-vitro </em>release studies of the synthesized conjugates of the series have shown good release results which indicates that synthesized conjugates release the parent drug (antimicrobial drugs) to the colon.<strong> Conclusion</strong>: Synthesized conjugates improve drug delivery to the intestinal region. Release studies result suggest that the drugs begin to release from the conjugates in the distal intestinal region and appreciable release in the colon has been observed.</p> 2022-07-26T00:00:00+00:00 ##submission.copyrightStatement## Targeting Amide Herbicides by KARI of Staphylococcus aureus- an in silico Analysis 2022-07-27T07:44:09+00:00 Rajasekhar Pinnamaneni Udaya Sri Puttagunta <p style="text-align: justify;"><strong>Background: </strong>Herbicides are classified either by toxicity or by mechanism of action, based on the chemical nature of the compound. Herbicides fall into two categories. Contact the herbicide and the transferred herbicide. Herbicides have been selected because they are highly toxic to plants and less toxic to animals and humans, but the main concern is the direct toxic effects of herbicides on animals. Since ketol acid reductoisomerase (KARI) is considered an acceptable target for most amide herbicides, this study conducted an <em>in-silico </em>analysis of KARI from <em>Staphylococcus aureus</em> against eight amide herbicides, obsessed with investigating by performing virtual molgro molecule docking. <strong>Materials and Methods:</strong> The <em>ilvC</em> gene encoding KARI from <em>Staphylococcus aureus</em> was amplified and its sequence and chimera were checked using the GenBank project`s CHIMERA CHECK program. It uses the BLAST algorithm and the GenBank database to compare the environment sequence with the GenBank sequence to find evolutionary relatives. Homology modeling of <em>Staphylococcus aureus </em>ketol acid reductoisomerase (KARI) was performed because its threedimensional structure revealed by either X-ray crystallography or NMR studies was not available. The generated model was used to repeat the energy minimization cycle many times using SPDBV software, and the final model was also used to perform docking analysis against the amide herbicide used in the inhibitor study. <strong>Results:</strong> The amplified DNA fragment containing 1005 base sequence BLAST hit, shows an absolute open reading frame encoding the <em>Staphylococcus aureus</em> protein KARI. PROSITE method shows active site residues Gln28, Leu79, Leu80, Asp82, Ala106, His107, Pro129, Lys130, Gly131, Pro132, Glu186, Asp190, Glu194, Cys199. The alignment of the protein sequence Ketol acid reductoisomerase (KARI) from <em>Staphylococcus aureus </em>and template &gt;1NP3A had a chain length of 327. The three-dimensional structure of<em> Staphylococcus aureus </em>ketol acid reductoisomerase (KARI) was predicted using SPDBV. The generated model used SPDBV software to repeatedly repeat the energy minimization cycle, so the final model received a stereochemical evaluation. After energy minimization, the energy of the protein model is 1.10 KJ / mol, which fits the Ramachandran diagram. Docking studies of <em>Staphylococcus aureus</em> ketol acid reductoisomerase (KARI) were initiated using the inhibitors reported in the literature. This model was then used to dock to various ligands, amides that act as herbicides. <em>In silico </em>models have demonstrated that this enzyme is effective against amide herbicides. <strong>Conclusion: </strong>On the idea of the docking scores, these ligands (amide herbicides) were assigned the results of favorable interactions between the compounds, and therefore the situation of KARI to search out more impregnable candidates out of the screened ligands, optimization of those amides should be extended further.</p> 2022-07-26T00:00:00+00:00 ##submission.copyrightStatement## Development and Validation of Prochlorperazine Maleate in Bulk and Pharmaceutical Dosage Form by UV Spectroscopic Method 2022-07-27T07:44:09+00:00 Hina Bagada Vishva Bhut Himaxi Parmar <p style="text-align: justify;"><strong>Objectives:</strong> Prochlorperazine maleate is an antipsychotic and antiemetic drug that is available as tablets on the market for oral administration. The main object of this research work is to develop and validate the easiest UV spectroscopic method for the determination of Prochlorperazine maleate for tablet formulation (marketed formulation).<strong> Materials and Methods: </strong>A simple, reproducible and efficient method for the determination of Prochlorperazine maleate in bulk and tablet formulations have been developed. The developed method is based on the estimation by UVVisible spectroscopy. In this method, 0.3M HCL was selected as the solvent. A Wavelength selected for estimation of Prochlorperazine maleate was 254 nm. <strong>Results:</strong> Linearity was found in the concentration range 2-16μg/ml (R<sup>2</sup>=0.9909). A recovery study was found to be 98.01-99.79% for Prochlorperazine maleate. The method was found to be precise as % RSD was low in repeatability, intermediate precision, and reproducibility. LOD and LOQ were found to be 0.58 and 1.75 respectively. <strong>Conclusion: </strong>The method was found to be very simple, and precise. It also had a good recovery. The Developed method can be used for further routine analysis and stability study of a Prochlorperazine maleate.</p> 2022-07-26T00:00:00+00:00 ##submission.copyrightStatement## The Development and Validation of Fast and Robust Stability Indicating RP-HPLC Method for Simultaneous Estimation of Azilsartan Medoxomil and Cilnidipine in Pharmaceutical Dosage Form 2022-07-27T07:44:10+00:00 Ravisinh Vikramsinh Solanki Ravi Bharatkumar Patel Rajeshkumar Kanubhai Patel Binal Manojkumar Patel <p style="text-align: justify;"><strong>Objectives: </strong>A selective, precise and accurate RP-HPLC stability indicating assay method has been developed for the simultaneous estimation of Azilsartan medoxomil and Cilnidipine in tablet dosage form. <strong>Materials and Methods:</strong> The efficient chromatographic separation of drug was achieved by using C<sub>18 </sub>(150mm×4.6mm, Agilent 5μm) Column at ambient temperature. Mobile phase contains triethylamine buffer (pH 3.5 adjusted with ortho-phosphoric acid) and acetonitrile (40:60 V/V). Flow rate of mobile phase 1.0 ml/min using isocratic mode .Wavelength selected at 249 nm by using photo diode array detector. <strong>Results: </strong>The retention time of Azilsartan medoxomil peak 1, Azilsartan medoxomil peak 2 and Cilnidipine were noticed to be 2.16 min, 3.90 min and 9.52 min respectively. The linearity range for Azilsartan medoxomil and Cilnidipine were found to be 50 -150 μg/ml and 12.5-37.5 μg/ml and percent recoveries were noticed to be 99.27±0.58 and 98.65±0.49 respectively. Various stress testing conditions such applied to the drug ingredients and drug formulation. The degradants and drugs efficiently separated by using enhanced chromatographic conditions. The developed method was validated as per recommendation parameters of International council on harmonization guideline Q2(R1). <strong>Conclusion:</strong> The validation parameters stated that the drug substances were efficiently separated from its degradants and developed method can be routinely applied for the simultaneous estimation of Azilsartan medoxomil and Cilnidipine in tablet formulation in a laboratory.</p> 2022-07-26T00:00:00+00:00 ##submission.copyrightStatement## Development and Characterization of Silymarin Phospholipid Complex for Improved Solubility, and Toxicological Evaluation in Experimental Animals 2022-07-27T07:44:10+00:00 Mandeep Kumar Singh Umesh Kumar Patil <p style="text-align: justify;"><strong>Objectives</strong>: The silymarin phytosome (SPY) was developed to improve the solubility and dissolution. The prepared phytosome was evaluated for hemolytic, membrane stabilization activity, and<em> in vivo</em> acute and subchronic toxicity. <strong>Materials and Methods: </strong>The toxicological evaluation was carried out by assessing its effects on liver, kidney, brain, lungs, heart and spleen in a rat model. In addition to confirmation of formation of phytosome, the physical-chemical characterization was done by FTIR, DSC, PXRD, and 1H NMR. <strong>Results: </strong>The optimized formulation has higher aqueous solubility of SPY compared to that of pure silymarin. The formulation also exhibited a significantly higher rate and extent of silymarin release in dissolution studies. The percent hemolysis for SPY was significantly less than silymarin. As a result, SPY can be concluded to be non-toxic and biocompatible for<em> in vivo </em>administration. SPY significantly inhibited hypotonic solutioninduced hemolysis in a dose-dependent manner. In acute oral toxicity, no treatment-related death or toxic signs were observed. The sub-acute test observations indicated that there are no treatment-related changes up to the high dose level. Food consumption, body weight, organ weight, hematological parameters, biochemical parameters and histopathological examination revealed no abnormalities. <strong>Conclusion: </strong>The study shows that SPY is a promising and viable strategy for improving the delivery of silymarin</p> 2022-07-26T00:00:00+00:00 ##submission.copyrightStatement## Formulation and Evaluation of Eudragit L- 100 based Nanoparticles of Senna for Treatment of Constipation 2022-07-27T07:44:10+00:00 Ashish Yashwantrao Pawar Ashvini Dhanraj Tapkir Jyoti Bramhesh Rao Rushikesh Pramod Dayama <p style="text-align: justify;"><strong>Background: </strong>The pharmaceutical industries are keen in development of new herbal bioactive molecules with an improved effect and less toxicity in order to replace synthetic drugs. Constipation is the most prevalent medical concerns. It’s estimated that one in five adults worldwide suffers from constipation. Hence, the demand of herbal laxatives is increasing worldwide. The purpose of this research work was to develop Senna nanoparticles with the help of Eudragit L100 an enteric coating polymer to provide site specific activity and to prevent degradation of Senna in acidic environment. <strong>Materials and Methods</strong>: Senna loaded nanoparticles were prepared by using emulsion solvent evaporation method. Different formulation has been formulated with varying concentration of Eudragit L-100 and constant aqueous and organic phase ratio (1:9). Drug and polymer compatibility study was analysed by FTIR. The prepared formulation was characterized by melting point, particle size, zeta potential, polydispersity index, vesical morphology and<em> in-vitro </em>drug release. <strong>Results</strong>: All the formulation batches shows particle size between 380.61 - 1061.71nm. The zeta of optimized batch (F5) was found to be -23.75mV. Entrapment efficiency of the entire prepared formulation batch in between 3.16±0.31- 55.18±0.35%. The <em>in-vitro</em> drug release shows maximum drug release i.e. 61.03% in 8 hrs which shows that release of drug prolonged and site specific due to use of enteric coated polymer Eudragit L100.<strong> Conclusion: </strong>The developed Senna loaded nanoparticles can provide site specific drug delivery. The polymer used in Senna Nanoparticles formulations shows efficient and targeted drug release as well as reduction in dose, dosing frequency and side effects</p> 2022-07-26T00:00:00+00:00 ##submission.copyrightStatement## Compression Coating Technique and its Formulation in Circadian Rhythm Activity with Chronotherapeutic Drug Delivery System 2022-07-27T09:45:12+00:00 Manjunath Pobbathi Nagaraj Avinash Kumar Seth Anand Kandkere Ravindra Kumar Vivekanandan Sundaramurthy <p style="text-align: justify;"><strong>Background: </strong>Circadian rhythms is a natural process that regulates the sleep wake cycle which is associated with several physiological, biochemical, endocrine, behavioural processes in humans and entrainment to light-dark cycle. The activity of Ramelteon is believed to contribute to its sleep-promoting properties and thought to be involved in the maintenance of the circadian rhythm underlying the normal sleep-wake cycle. A tablet can be given before 2 hr of bed time, so the Ramelteon drug shows its effect throughout the night by releasing the active content with lag time followed by sustained action to promote the sleep. <strong>Materials and Methods</strong>: Chronotherapeutic drug delivery system were prepared by compression coating technology using pH independent, hydrophilic and hydrophobic polymers. <strong>Results: </strong>Drug excipient compatibility indicated that the Ramelteon Active pharmaceutical ingredient (API) is compatibility with the excipients proposed. The X-ray Diffraction (XRD) studies indicated that the crystalline form of the Ramelteon API existed in the finished formulation. <strong>Conclusion: </strong>The core tablets containing Eudragit RSPO 10mg/tablet and ratio of Ethyl cellulose: Hydroxy propyl methyl cellulose (HPMC) of 70:30 in the outer coating material yielded a desired lag time of 2 hr and drug release for a period of 4 hr to achieve a chronotherapeutic drug delivery system. Ramelteon is an excellent candidate in designing chronotherapeutic drug delivery systems and further<em> in vivo </em>studies can be explored in the treatment of circadian rhythm with sleep wake cycle disorders.</p> 2022-07-26T00:00:00+00:00 ##submission.copyrightStatement## Inhibition by Ascorbate among Phosphofructokinase-1, Aldolase, Enolase, and Lactate Dehydrogenase in Rabbit Muscle 2022-07-27T07:44:11+00:00 Anita Ricablanca Ami Abbott Fatimata Sonago Montserrat Garcia Rachel Primacio Eric Patten Mudassar Iqbal Arain Eduardo Fricovsky <p style="text-align: justify;"><strong>Background: </strong>These studies examined mutual protective relationships among rabbit muscle aldolase, enolase, phosphofructokinase-1 (PFK-1) and LDH from inhibitions by ascorbate (AA). It was proposed earlier that specific inhibitions of PFK-1 and LDH by AA faciltated glycogen storage in resting muscle by inhibiting glycolysis. <strong>Materials and Methods:</strong> The L-ascorbate (AA), L-ascorbyl dibutyrate (AADB), L-ascorbyl dipalmitate (AADP), L-ascorbyl palmitate (AAP), and L- ascorbyl stearate (AS) are shown in Figure 1 and were obtained from TCI and Alfa Aesar. Unless otherwise stated, all enzymes come from rabbit and all experimental temperatures were 25°C, pH 8.0. <strong>Results</strong>: Rabbit muscle enolase was examined for its protective effect on other rabbit muscle glycolytic enzymes against inhibitions by ascorbate (AA) and some AA-faty acid derivatives. The IC<sub>50</sub> values of enolase by ascorbate (AA) and IC<sub>50 </sub>values of AA-fatty acid derivatives were compared to estimate inhibition potency. For example, ascorbyl dipalmitate (AADP) was 156 times more inhibitory to enolase than AA. It was previously shown that rabbit muscle aldolase prevented LDH activity loses due to AA inhibition and prevented PFK-1 activity losses due both to dilution and AA inhibition; enolase was found to have the same effects as aldolase. Additionally, PFK-1 prevented enolase and LDH inhibitions by AA. LDH did not prevent enolase or PFK-1 from inhibition by AA. LDH did stimulate enolase activity but not PFK-1 activity. <strong>Conclusion:</strong> The results suggest that interactions among glycolytic enzyme serve to mutually protect one another from activity losses. The inhibition properties of the AA-fatty acid derivatives are discussed in relation to their possible roles in cancer and diabetes.</p> 2022-07-26T00:00:00+00:00 ##submission.copyrightStatement## Comparisons of Phosphofructokinases-1 from Rabbit, Chicken, and Fish 2022-07-27T07:44:11+00:00 Patricia Gaitan-Hahn Anita Ricablanca Ami Abbott Jessica Chadwick Alicia Thomas Nathalia Cruz Alice Deng Leah Ordinanza Mudassar Iqbal Arain Eduardo Fricovsky <p style="text-align: justify;"><strong>Background:</strong> Previous studies suggested that glycogen storage was facilitated by ascorbate inhibition of phosphofructokinase-1 (PFK-1) in resting mammalian muscle; these studies showed that purified PFK-1 from fish or chicken muscle has properties similar to PFK-1 from mammalian muscles.<strong> Materials and Methods:</strong> The enzymes utilized in the assay systems came from Sigma-Aldrich Co. Rabbit (<em>Oryctolagus cuniculus</em>) muscle G-actin (A 2522) was free of aldolase, LDH (EC or AK (EC activity and rabbit muscle aldolase (EC was free of AK (EC and LDH activity. Rabbit muscle PFK-1 (RPFK-1), chicken (Gallus gallus) muscle PFK- 1 (CPFK-1) and Pacific red snapper (Lutjanus peru) muscle PFK-1 (FPFK-1) used in these tests were prepared from frozen tissues with modifications of a method. AK, LDH, and aldolase activity were absent in purified FPFK- 1 and CPFK-1 preparations. <strong>Results:</strong> It can be shown that the following enzymes associated with glycolysis are not inhibited by 0.1 M ascorbate under our conditions: rabbit muscle aldolase (EC; rabbit muscle glyceraldehyde 3-phosphate dehydrogenase (EC; rabbit muscle phosphoglucose isomerase (EC; rabbit muscle pyruvate kinase (EC; yeast hexokinase (EC 2,7.1.1); and yeast 3-phosphoglyceric phosphokinase (EC Rabbit muscle enolase (EC4.2.1.11) is inhibited under our conditions. <strong>Conclusion:</strong> In summary, FPFK-1 and CPFK-1, possess characteristics and behaviors similar to RPFK-1, e.g., losses of activities due to dilutions and protections of some of these activity losses by rabbit muscle aldolase. These interactions of a mammalian aldolase with fish and a bird PFK-1’s suggests a conservative evolutionary relationship among aldolases and PFK-1’s.</p> 2022-07-26T00:00:00+00:00 ##submission.copyrightStatement## Tephrosia purpurea Ameliorates Oxidative and Histological Alterations Induced by Aflatoxin B1 in Rats 2022-07-27T07:44:11+00:00 Shamli S Gupte Arti Rathour Divya Gupta Richa Soni Sadhana Shrivastava Monika Bhaduria Satendra Kumar Nirala Shubham Singh Anjali Sharma Deepa Yadav Samrat Rakshit Sangeeta Shukla <p style="text-align: justify;"><strong>Background: </strong><em>Tephrosia purpurea</em> (TP), commonly known as wild indigo, is traditionally used in treatment of splenomegaly. It is an important ingredient of various Ayurvedic medicines used in treatment of liver diseases. Objectives: Thus, the study was undertaken to investigate the hepatoprotective efficacy of ethanolic extract of TP against Aflatoxin B1 (AFB1) induced liver injury. <strong>Materials and Methods: </strong>The ethanolic extract of TP was prepared by Soxhlet extraction method. Presence of polyphenols and antioxidant potential were assessed. The antiproliferative activity of extract was tested on HepG2 cells using MTT assay. For <em>in vivo</em> studies female Wistar rats were randomly divided into 6 groups with 6 animals in each. The entire regime was of 33 days. AFB1 was administered at 200 μg/kg dose and TP was administered at three different doses (100, 200 and 300 mg/kg). 24 hr after last treatment the animals were euthanised and liver and blood samples were collected. <strong>Results:</strong> 45.77± 2.53 μg/ ml IC50 of extract was seen on HepG2 cells. A significant elevation in serum transaminases, triglycerides (TG) and LPO was seen after AFB1 intoxication. Whereas decline in activities of GSH, SOD, CAT, G6Pase and ATPase were observed. Treatment with different doses of TP restored its activities towards normal indices. Maximum recovery was seen with 300 mg/kg dose of TP.<strong> Conclusion: </strong>It may be concluded that TP possess hepatoprotective efficacy against AFB1 induced oxidative injury and it may prove to be of clinical use after further studies</p> 2022-07-26T00:00:00+00:00 ##submission.copyrightStatement## Nephroprotective Activity of Ethanolic Extract of Alternanthera sessilis Leaves in Gentamicin-induced Nephrotoxicity in Wistar Albino Rats 2022-07-27T07:44:12+00:00 V. V. Rajesham Ruqaiya Jabeen Mitta Raghavendra P. Roshan Ali T. Rama Rao <p style="text-align: justify;"><strong>Background:</strong> Renal disease is a significant issue of global proportions and renal damage is very prevalent as the kidney has the ability to excrete toxic substances to assess the protective impact of the Ethanolic extract of <em>Alternanthera sessilis</em> Linn. (EEAS) plant leaves against gentamicin induced nephrotoxicity in rats. <strong>Materials and Methods: </strong>Nephroprotective activity was assessed by inflicting gentamicin (80 mg/kg) in all groups; acute kidney dysfunction is proven by the vital increment of blood serum creatinine, uric acid, BUN and decline in the total protein, albumin, and globulin with various histological damages.<strong> Results:</strong> Treatment with the <em>Alternanthera sessilis</em> has appeared critical dosage subordinate change at the measurements of 100 and 200mg/kg by securing the kidney from oxidative stretch. It is additionally recognized that treatment with <em>Alternanthera sessilis </em>essentially brought down the level of serum creatinine, uric acid, BUN and increment within the add up to protein, egg whites, globulin when compared to illness gather. Nephroprotective action of EEAS was found when compared with the standard bunch (Vitamin E 250 mg/kg) and control bunch against the infection gather creatures in parameters counting creatinine, urea, uric corrosive, Blood Urea Nitrogen (BUN), add up to protein, egg whites and globulin. The histopathological considers were moreover proving the defensive impact of EEAS. <strong>Conclusion: </strong>From the above results it was concluded that the ethanolic extract of <em>Alternanthera sessilis</em> offers nephroprotection.</p> 2022-07-26T00:00:00+00:00 ##submission.copyrightStatement## Antidiabetic Activity of an Alkaloid (4a-Methyl-5-(6-Methylhept- 5-En-1-Yl)Octahydro-1H-Cyclopenta[A]Pyridazine) Isolated From Lumnitzera racemosa in Streptozotocin-Induced Diabetic Wistar Rats 2022-07-27T07:44:12+00:00 . Ranjana Deepak Kumar Singh Bhaskar Laxman Jadhav <p style="text-align: justify;"><strong>Background: </strong>Diabetes mellitus is a metabolic disorder that causes millions of deaths throughout the world every year, and today also its incidence is on the increase. Many antidiabetic drugs are available in the pharmaceutical market, but drawbacks related to them had forced the researcher’s attention to switch towards naturopathy. The study aimed to isolate and evaluate the antidiabetic principle from the mangrove plant <em>Lumnitzera racemosa </em>leaves. <strong>Materials and Methods:</strong> The active principle was isolated using column chromatography and identified with high-performance liquid chromatography, and further structure elucidation was done by FT-IR, LCMS, NMR, and elemental analysis. The antidiabetic activity of that isolated compound was monitored using <em>in vitro </em>α-amylase and α-glucosidase inhibition and<em> in vivo </em>STZ-induced diabetic rat models.<strong> Results: </strong>The isolated compound showed potent antidiabetic activity by inhibiting α-amylase and α-glucosidase with IC50 values of 30.23 and 0.022 mg/ml, respectively. Furthermore, the isolated compound administration (250 and 500 mg/ml BW) in STZ-induced diabetic rats has exhibited a significant dose-dependent decrease in blood glucose levels. Besides this, the haematological findings, biochemical, and histopathology of the isolated compound showed comparable results to that of standard glibenclamide, indicating the protective role of the compound against any damage to the pancreas, liver and kidney. HPLC and different spectroscopic analyses revealed that the isolated compound is 4a-methyl-5-(6-methylhept-5-en-1- yl)octahydro-1H-cyclopenta[a] pyridazine, which belongs to the alkaloid class of the secondary metabolites. <strong>Conclusion: </strong>Data obtained states that the alkaloid isolated from<em> L. racemosa</em> leaves possess significant antidiabetic activity in both<em> in vitro </em>and <em>in vivo </em>models.</p> 2022-07-26T00:00:00+00:00 ##submission.copyrightStatement## Evaluation of Diuretic and Laxative Potential of Onosma bracteata Wall.: A Species of the Controversial Drug ‘Gojihva’ 2022-07-27T07:44:12+00:00 Udaykumar Girdharlal Vegad Devang Jagdishbhai Pandya <p style="text-align: justify;"><strong>Background:</strong> <em>Gojihva or Gaozaban</em>, an Ayurvedic cum Unani Medicinal plant described with various properties, including diuretic activity. Onosma bracteata Wall. is considered the official species of <em>Gojihva </em>in Ayurveda and is one of the species considered Unani <em>Gaozaban.</em> <strong>Materials and Methods: </strong>The plant was subjected to physicochemical evaluation, sequential extraction, HPTLC profiling, and phytochemical screening. The diuretic and laxative activity of sequential methanol and water extracts of <em>O. bracteata </em>Wall. at a dose of 100 mg/kg and 200 mg/kg of body weight per oral was measured in Wistar rats in two separate experiments. <strong>Results:</strong> Preliminary phytochemical investigation and TLC profiling revealed the presence of flavonoids/hydroquinone/phenolics in methanol extract. Additionally, elemental analysis of plant material detected Potassium (K) at a level of 672.12 ppm. The methanol extract at doses 100 mg/kg (1.65 mL ± 0.19) and 200 mg/kg (2.00 mL ± 0.28) and aqueous extract at dose 200 mg/kg (1.63 ± 0.12) showed highly significant diuretic activity (p&lt;0.0001) at 6 h compared to standard (0.67 mL ± 0.21). Whereas the aqueous extract of the plant showed mild constipation action. <strong>Conclusion: </strong>The literature search revealed that the diuretic potential of the methanolic extract could be attributed majorly to carbonic anhydrase inhibitory activity of constituent compounds like caffeic acid, rosmarinic acid, p-hydroxybenzoic acid, artitrichin, salvianolic acid, and coumarins, in addition to natriuretic, Ca<strong><sup>2+</sup></strong> sparing activity, and increased renal excretory function. The milder diuretic action of the aqueous extract can be due to the presence of potassium salts in aqueous extracts. Thus, the traditional use of <em>Gojihva </em>as a diuretic is established on a phytochemical basis. Further pharmacological and phytochemical investigations of Methanol extract may reveal novel compounds with diuretic potential</p> 2022-07-26T00:00:00+00:00 ##submission.copyrightStatement## Silymarin, Quercetin and Hesperidin Combination Ameliorates Learning and Memory Deficit in 3 Nitro Propionic Acid Induced Rat Model of Huntington’s Disease 2022-07-27T07:44:12+00:00 Arti Akash Bhimanwar M M Ghaisas R V Shete <p style="text-align: justify;"><strong>Introduction:</strong> Huntington’s disease is considered as the autosomal dominating with progression of neuro-degeneration with decreased cognitive function and behaviour changes. Bioflavonoids promote memory, learning, and cognitive function. The present study aims to summarize the synergistic effect of Silymarin, Quercetin and Hesperidin on ability to in 3-nitropropionic acid (3-NP) induced rat model of Huntington’s disease (HD). <strong>Materials and Methods: </strong>Learning and memory deficits were induced in male Wistar rats through intraperitoneal administration of 3-NP. Bodyweight was taken on days 1<sup>st</sup>, 7<sup>th</sup>, 14<sup>th</sup>, and 21st post-treatment. Novel object recognition test (NORT) and elevated plus maze (EPM) were performed on days 21<sup>st</sup> and 22<sup>nd</sup>. Animals were sacrificed on day 22 for acetylcholinesterase (AChE) estimation, brain weight assessment, and histopathological study. <strong>Results:</strong> Administration of 3-NP at a dose of 10 mg/kg body weight for 21 days significantly induced learning and memory deficit similar to HD. It reduced body and brain weight, memory retention, and recognition index with enhanced function of acetyl cholinesterase in the brain striatum. Silymarin and Hesperidin as monotherapy significantly restored recognition index and memory loss induced by 3NP due to reduced neuronal damage and apoptosis in the brain striatum, Quercetin and Silymarin restored body weight and relative brain weight because of an increase in muscle weight and reduced brain atrophy.<strong> Conclusion: </strong>All bioflavonoids restored AChE activity, but their combination was better compared to individual drug effects. The current investigation proved that a combination of Silymarin, Quercetin, and Hesperidin is effective in the restoration of ability to learn and memory because of HD compared to monotherapy</p> 2022-07-26T00:00:00+00:00 ##submission.copyrightStatement## L-carnitine Protects Cisplatin Induced Liver Fibrosis in Experimental Animals via Reducing Oxidative and Nitrosative Stress 2022-07-27T07:44:12+00:00 Vikram Nimbalkar Niraj Vyawahare <p style="text-align: justify;"><strong>Background:</strong> The aim of the present study was to examine the protective potential of L-carnitine against Cisplatin-induced liver fibrosis in experimental models. <strong>Materials and Methods: </strong>The rats were randomly divided into five groups, each containing an equal number of animals (n = 6). Repeated doses of Cisplatin were used to promote liver fibrosis, and serum parameters like aspartate aminotransferase (AST), alanine transaminase (ALT), total bilirubin (TB), and albumin were assessed, as well as hepatic hydroxyproline (HP), reduced glutathione (GSH), and malondialdehyde (MDA), Superoxide dismutase (SOD), and pro-inflammatory cytokines. A Western blot was used to quantify iNOS expression, and liver tissue was also processed for histological examination (H&amp;E staining). <strong>Results:</strong> In this investigation, we discovered that Cisplatin decreased body and liver weight in rats, whereas L-carnitine administration resulted in normal body and liver weight. Cisplatin rats had higher levels of serum parameters (AST, ALT, total bilirubin) as well as oxidative parameters like GSH, MDA, and inflammatory-cytokines. Treatment with L-carnitine reduced oxidative stress and suppressed the release of cytokines in a dose-dependent manner, as well as providing protection against fibrosis. In cisplatin-treated rats, iNOS expression was found to be 1.8 times higher. Furthermore, increased iNOS expression was dose-dependently reduced after treatment with L-carnitine. <strong>Conclusion:</strong> According to the findings, L-carnitine has a protective effect against Cisplatin-induced liver fibrosis.</p> 2022-07-26T00:00:00+00:00 ##submission.copyrightStatement## Influence of Polygonum minus Aqueous Extract on Monoamine Oxidase-A Transcriptional Activators KLF-11 and SIRT1 Levels in the Hippocampus of Stress-induced Depressed Mice 2022-07-27T07:44:13+00:00 Muhammad Irfan Bashir Nur Hidayah Kaz Abdul Aziz Dzul Azri Mohamed Noor <p style="text-align: justify;"><strong>Background: </strong>Monoamine oxidase-A (MAO-A) enzyme is responsible for the breakdown of monoamines (serotonin and norepinephrine). MAO-A is also a target to treat the depressive disorders. Kruppel-likefactor11(KLF11) and Sirtuin1(SIRT1) are the main transcriptional activators of MAO-A. <em>Polygonum</em> <em>minus</em> (<em>P. minus</em>) aqueous extract showed some neuroprotective properties in previous studies like improved memory and positive mood. The aim of current study was to evaluate the effects of <em>P. minus</em> aqueous effects on KLF11 and SIRT1 levels in hippocampus of stressed mice. <strong>Materials and Methods</strong>: Balb/c mice (22g-26g) were used in this study and <em>P. minus </em>aqueous extract was administered for 8 weeks with three different doses (<em>P. minus</em> 50mg, P. minus 100 mg and<em> P. minus</em> 200mg) in different groups. Amitriptyline 20 mg was used as positive control antidepressant. Chronic ultra-mild stress protocol was used for 6 weeks to induce the depression among mice groups except control group.<strong> Results: </strong>The results showed that all doses of<em> P. minus </em>reduce the KLF11 level significantly but only <em>P. minus </em>200mg showed reduction in SIRT1 level in hippocampus of mice significantly.<strong> Conclusion:</strong> It is concluded that <em>P. minus </em>aqueous extract treatment showed a significant reverse in an elevated level of KLF11 and SIRT1 in hippocampus of stressed mice after treatment of 8 weeks</p> 2022-07-26T00:00:00+00:00 ##submission.copyrightStatement## The Impact of an Educational Intervention on the Skill of Community Pharmacists in the Use of a Pressurized Metered-dose Inhaler: A Covert Simulated Patient Approach in Pakistan 2022-07-27T07:44:13+00:00 Sara Shahid Fahad Ahmed Fahad Ahmed Amna Bajwa Muhammad Ans Anosh Sana Sameen Abbas Asma Fareed Khan Aiman Mahmood Qandeel Rafi Shakeel Ahmad Asifa Anwar Rabeel Khan Gul Shahnaz Asad Majeed Khan <p style="text-align: justify;"><strong>Introductio</strong>n: Metered-dose inhalers are the most widely prescribed and dispensed inhaler devices worldwide for the management of asthma. The present study aimed to access the impact of educational intervention on the competency of community pharmacists of Islamabad, Pakistan regarding the pressurized metered-dose inhaler (MDI) technique. <strong>Materials and Methods</strong>: The intervention involved educating pharmacists practically through placebo inhalers and theoretically through literature brochures; based upon the “National Asthma Education and Preventive Program” inhaler technique. A total of 100 pharmacists were recruited from the rural and urban sectors of Islamabad. A covert simulated patient approach was used to evaluate the inhaler technique of pharmacists. Type of pharmacy, education status of pharmacists and the influence of already received training on the use of inhaler devices were the factors that demonstrated a significant positive association with the competency of pharmacists.<strong> Results:</strong> McNemar test was applied for pre and post-intervention intragroup comparisons to further access categorical variables. A p-values &lt;0.05 were considered statistically significant. The competency of pharmacists increased significantly from 24% before intervention to 33% after intervention (p&lt;0.001). <strong>Conclusion: </strong>Originally, the inhaler technique competency of the majority of pharmacy professionals was observed to be inappropriate. However, the educational intervention proved to be effective in substantially enhancing the skill of community pharmacists regarding the MDI technique.</p> 2022-07-26T00:00:00+00:00 ##submission.copyrightStatement## Formulation and Evaluation of Timolol Maleate Proniosomal Gel for Ocular Drug Delivery 2022-07-27T07:44:13+00:00 Jayatheertha S Lokapur Prakash S Goudanavar Arpitha J Lokapur Ankit Acharya Sandip A Murtale <p style="text-align: justify;"><strong>Introduction: </strong>The objective of this task is to succeed with the trial of an ocularly efficient Timolol maleate formulation produced from prolonged proniosomal gel niosomes to get significant therapy for glaucoma.<strong> Methods</strong>: Cholesterol, Lecithin, Span 60, Brij 72, and Tween 80 in various concentrations were used to create Timolol maleate loaded proniosomal gel derived niosomes utilizing the phase coacervation method. Found on these outcomes of entrapment efficiency and <em>in-vitro </em>release, an optimised batch of proniosomal gel-produced niosomes was chosen. By spreading proniosomes in an<em> in-situ</em> gelling method, timolol maleate proniosomal gel-derived niosomes were created. Fourier transforms infrared spectroscopy (FTIR) experiments confirmed each interaction study. Wetting agent with additive effects on entrapment efficiency along with<em> in-vitro </em>drug release manner based on proniosomal gel-produced niosomes was investigated. Cholesterol, Lecithin, Span 60, Brij 72, and Tween 80 in various quantities were used in a coacervation technique, by dispersing proniosomes in an<em> in-situ </em>gelling method, a timolol maleate proniosomal gel was created.<strong> Results: </strong>The FTIR analyses revealed no signs of interaction between the medicine and the excipients, indicating that they are compatible. At the end of 12 hr, formulations T2 and T10 had 99.98 percent and 99.90 percent drug release, respectively. <strong>Conclusion:</strong> Starting with these findings secured, it can be closed this one proniosomal gel derived niosomes might be a satisfactory alternative to conventional eye drops as they exhibited elevated penetrability with sustained-release actions.</p> 2022-07-26T00:00:00+00:00 ##submission.copyrightStatement## Measuring Medicine Prices and Availability of Commonly used Essential Medicines using WHO/HAI Methodology in Hyderabad, India 2022-07-27T07:44:13+00:00 Sai Latha K Abhinaya P Parimala G Lakshmi PK <p style="text-align: justify;"><strong>Objectives: </strong>Access to health care is a basic right of population. Essential medicines are those which satisfy the priority of health care needs and intended to be available at all times. Hence prices and availability need to assess periodically. The objective of the study was to measure the variation in prices of selected medicines, to measure the availability of some selected medicines used for treating common diseases/ailments and to compare the prices and availability of medicines among the sectors. The present survey is conducted for 20 essential medicines in Hyderabad, Telangana. <strong>Methods</strong>: Medicines were selected based on the criteria of WHO/HAI methodology. Data was collected during October 2019 to March 2020 for originator brands and lowest priced generics in 60 medicine outlets. Prices were compared to international reference prices and expressed as median price ratio. Percent availability computed only on the day of data collection. <strong>Results: </strong>Median MPRs for originator brands and lowest priced generics were 2.20 and 1.53 in independent outlets, 2.20 and 1.61 in chain pharmacies respectively. Median MPR for generics in Jan Aushadhi Kendra was 0.38 i.e., all available medicines were priced less than international reference prices. Availability was 95.8%, 95.4% and 67.5% for generics and 12% and 13.3% for originator brands respectively. <strong>Conclusion: </strong>The survey revealed reasonable prices and high availability in private sectors but in JanAushadhi Kendra, prices are flattened with good availability. The maximum applicable Goods and Services Tax rate is 12% for medicines under price control and life-saving drugs resulted in 2.3% increase in tax rate ultimately causing burden to patients. Government should ensure certain policies about importance of generic drugs and their availability in Jan Aushadhi Kendra.</p> 2022-07-26T00:00:00+00:00 ##submission.copyrightStatement## Congenital Hydrocephalus with Aqueductal Stenosis: A Rare Condition Case Report 2022-07-27T07:44:14+00:00 Rajeshwari Pasupula S. Bhanu Uday Sankar Sreya Kosanam Ch Naga Priya Ch Varudhini Devi Bhimavarapu Sai Deepika <p style="text-align: justify;">Congenital Hydrocephalus is due to buildup of excess cerebrospinal fluid in the brain at birth. Fluid buildup leads to neurological and psychological damages to the child. Aqueductal stenosis means a narrowing the passageway between the third and fourth ventricles. In this case report, Ventriculoperitoneal shunt is placed to relieve the pressure, but was removed due to Meningitis. As per review of literature, incidence of shunt failure in infants below 2 years is 5-12% and with more than 60% mortality rate.</p> 2022-07-26T00:00:00+00:00 ##submission.copyrightStatement## Research Tools: Endnote Click (Formerly Kopernio): Access millions of Research Paper PDFs 2022-07-27T08:47:57+00:00 KK Mueen Ahmed <p style="text-align: justify;">Endnote Click is a new, free research tool from Clarivate Analytics that allows authors to quickly find and download PDFs of research papers. By indexing the full text of millions of research papers, Endnote Click makes it easy to find the papers needed. Endnote Click is a new research tool that allows researchers to access millions of research paper Portable document formats (PDFs). It’s the perfect way to keep up with the latest research in a different field. Endnote Click is available for free, and it’s easy to use. By just entering keywords and Endnote Click will search through millions of research paper PDFs to find the ones most relevant to the search. Endnote Click is a great way to stay up to date on the latest research in different fields. Endnote Click can be a useful tool for students and professionals who are researching a paper. It allows accessing millions of research paper PDFs from around the world. This can be a great way to find new and interesting papers to read, as well as to get ideas for research. Endnote Click can also help to organize papers and keep track of progress. In addition to providing access to millions of research paper PDFs, Endnote Click also offers various other services that can be useful for students and researchers. These include a reference manager, citation tool, and a bibliographic database. With these tools, researchers can easily organize their research, track their citations, and create bibliographies. Endnote Click makes research easier and more efficient.1</p> 2022-07-26T00:00:00+00:00 ##submission.copyrightStatement##